The principal objective of this project is to study the intraneural paired helical filaments (PHF) which are the morphological hallmark of Alzheimer's presenile/senile dementia. We will continue to isolate and characterize the PHF with respect to peptide maps, end group analysis, colchicine and nucleotide binding, and antigenic determinants. These findings will be used to compare the PHF with normally occurring neurotubules, and neurofilaments. Attempts will be made to isolate the aluminum-induced neurofilaments from rabbits with experimental aluminum encephalopathy, and to compare them with the paired helical filaments, the normal neurofilaments and the neurotubules. Synthesis and turnover of neuronal proteins in general, and neurofilament and neurotubule proteins in particular will also be studied in rabbits with induced aluminum encephalopathy. Using atomic absorption method, aluminum content will be determined in neurons isolated from areas of the brain rich in neurofibrillary tangles, minimally affected areas of the same brains, and in neurons isolated from control brains. Utilizing antisera raised in rabbits against each of the neurofibrillary proteins, the cross reactivity of these proteins will be determined. The cytological localization of the PHF protein to PHF by immunohistofluorescence and immunoperoxidase labeling techniques will also be demonstrated. The methods of procedure outlined in this grant proposal include biochemical and immunological methodology, light and electron microscopic studies. Alzheimer's presenile/senile dementia is one of the greatest financial burdens on society today. This research offers the possibility of opening fruitful studies of the biochemical defects in this disease.